Official Title

Summary:

This research project intends to look at the effect that a certain type of freezing
injection, called a paravertebral block, has on the pain after an operation for breast
cancer, the amount of pain relief that is needed and the side effects from this pain relief.
The hypothesis is that the paravertebral block, in combination with a general anesthetic will
reduce both pain scores and the amount of strong pain killers (opioids) that is needed. This
will reduce the side effects of the pain killers such as nausea and vomiting.
This will be assessed by comparing it a general anesthetic with pain killers given through
the intravenous (IV) as is routine practice. Patients requiring breast cancer surgery, who
agree to be involved in the trial, will be randomly allocated into two groups: both groups
will receive a block, then a standardised and optimised general anesthetic. In one group
however the block is simply a small injection under the skin (a sham block), whereas the
other group will receive a proper paravertebral block prior to this. Both groups will receive
opioids as necessary, depending on both their bodies reaction during the surgery and their
pain scores when they wake up.
The paravertebral block is a very safe procedure with a very low side effect profile, and
many studies have shown a benefit in breast cancer surgery. The investigators would like to
assess this in our own practice. The block is normally inserted under some light sedation,
with freezing into the skin initially. It is normally very well tolerated. The sham block
will also be performed under light sedation and freezing into the skin. The patients will not
be able to tell whether they are having the sham block or the paravertebral block, because
both are very well tolerated. There are no potential complications from the sham block.

Trial Description

Primary Outcome:

Post-operative analgesia consumption

Secondary Outcome:

Post-operative pain

Nausea/vomiting

Pain upon movement

Intraoperative opioid requirement

Background Surgery for breast cancer can lead to a number of issues in the perioperative
period. Both acute and chronic post-surgical pain are commonly encountered problems, with
evidence that the degree of acute pain influences the likelihood of chronic pain.
Post-operative nausea and vomiting (PONV) are also common, given the predominantly female
surgical population and the requirement for opioid analgesia.
Paravertebral block (PVB) is an effective means of providing analgesia for mastectomy. A
recent meta-analysis5 suggested that there is considerable evidence that paravertebral blocks
with or without a general anesthetic (GA) provide superior post-operative analgesia to breast
surgery operations done with a GA alone. There is also a reduced need for rescue analgesia
and reduced opioid-related side effects. The results of this meta-analysis may be influenced
by publication bias, and the results are difficult to interpret because the lack of
standardisation of technique (single level injection, multi-level injection or continuous
blockade via a catheter inserted into the paravertebral space) and the variety of the type
and dosage of the local anesthetics used for the PVB. The meta-analysis does suggest that PVB
is an effective technique for mastectomy with a minimal complication rate.
In our institution, the most common form of analgesia for mastectomy patients is systemic
opioid analgesia. However, in the last two years, single level PVBs have been used with
increasing frequency and reliable success. This is due in part to the use of
ultrasound-guidance for placement of the PVB, which is a relatively simple technique with a
well-defined end-point. The investigators have been using 0.2% ropivacaine, which was only
mentioned in one study of the meta-analysis and was used with a multiple injection technique.
The majority of studies used 0.5% bupivacaine, and most of these studies used PVB as the sole
anesthetic technique. The next most common local anesthetic used was ropivacaine 0.5%, and
this was more frequently used with multi-level injections. As the investigators use a single
level injection in combination with a GA, these studies are not completely relevant to our
current practice.
In this study, the investigators will compare PVB using Ropivacaine 0.2% combined with a GA,
to GA alone with systemic analgesia.
Purpose The purpose of this study is to compare GA with systemic analgesia to GA with PVB.
The parameters examined will be pain scores, perioperative opioid analgesia requirement, and
PONV. Complications of PVB will also be examined.
Hypothesis GA plus PVB will reduce pain scores at rest and on movement, the need for rescue
analgesia, and the incidence of PONV.
Study population:
Patients with Breast Cancer listed for surgery at the University Hospital of Alberta and the
Cross Cancer Hospital. The study will commence following ethical approval.
Power calculations are required to determine recruitment numbers.
Methods:
The study population will be identified by the breast surgeons in their clinic, and potential
recruits will be provided with information regarding the study protocol and techniques on
that day. Patient consent will be obtained by the investigating team (study coordinator or
anesthesiologist) on the day of surgery. Randomisation of participants will also occur at
this time.
For those randomised to the PVB group, a block will be placed under sedation by one of the
Acute Pain Service experienced in paravertebral blocks. The sham block group will receive
some subcutaneous saline under ultrasound guidance, mild sedation and local anesthetic skin
infiltration. All patients will receive a standard GA and post-operative protocol.
Patients who do not wish to enrol in the study will receive a general anesthetic plus
appropriate analgesia according to the operating room anesthesiologist. No data will be
recorded, apart from the fact that they declined to take part in the study.
Primary outcome measures:
1. Post-operative analgesia requirement
Secondary outcome measures:
1. Maximum pain score in the 24 hours following surgery
2. Incidence of PONV requiring additional treatment.
3. Maximum pain score in recovery at rest and on shoulder abduction
4. Incidence of perioperative complications
5. Intraoperative opioid requirement
Safety Concerns:
Paravertebral blocks have been used for many years. Major complications are rare. The
investigators hypothesise that ultrasound should reduce these complications further as
anatomical structures are directly visualized.
Major concerns:
1. Pleural puncture and pneumothorax
2. Paravertebral hematoma
3. Intrathecal local anesthetic injection
4. Local anesthetic toxicity
5. Paravertebral infection
Minor concerns:
1. Block failure
2. Epidural spread of local anaesthetic
3. Low blood pressure
4. Horner's Syndrome
5. Injection site hematoma
Study Protocol
1. Paravertebral block The patient will be reviewed by the study investigator then moved to
the block area.
Paravertebral block will be sited following intravenous access, commencement of IV
crystalloid, and standard patient monitoring. A time out will confirm side of surgery
which will be marked.
Sedation and oxygen will be commenced prior to insertion of the block. The patient will
be positioned in the seated position with the side of surgery clearly marked. The level
between the transverse processes of T2 and T3 will be identified using ultrasound, then
injection of 1% lidocaine to skin. Tissue movement and hydrolocation will confirm block
needle position, with anterior movement of the pleura being the end point. Once this is
reached, 20cc of ropivacaine 0.2% will be injected. The patients will progress to the
standard anesthetic protocol.
2. Sham block The patient will be taken to the block area, where the IV and monitors will
be connected as usual. Sedation and oxygen will be commenced. The sham block will occur
as described for the true paravertebral block, including injection of lidocaine to
anesthetize the skin, except that a small amount of normal saline (volume of which will
be left to the anesthesiologist's discretion) will be injected subcutaneously instead of
injection of ropivacaine next to the nerve.
On the operating table, routine plus Bispectral (BIS) monitoring will be attached. If no
midazolam has been administered, 0.03mg/kg will be given intravenously (IV). Fentanyl 1
microgram per kilogram IV will be given. Propofol will be titrated to allow insertion of
a laryngeal mask airway (LMA), unless intubation is necessary. This will be at the
discretion of the operating room anesthetist. Propofol via pump will be given at
200mcg/kg/min, aiming for a BIS score between 35 and 50. Phenylephrine or ephedrine can
be titrated as necessary to maintain a mean arterial blood pressure above 60, or greater
than 75% of the starting mean pressure. Spontaneous ventilation with pressure support
will be used to maintain an end tidal carbon dioxide level of less than 50mmHg. Fentanyl
(25mcg boluses) will be titrated to a respiratory rate of 8

15 breaths per minute.
Ketorolac 15mg and Ondansetron 4mg IV will be given unless contra-indicated.
3. Post-operative Protocol
All patients will receive standard post-operative orders:
Patients will receive tramacet 3 tablets PO. Morphine 2mg IV will be given every 5
minutes as required for pain reported on the Numeric Rating Scale (NRS) of greater than
5. If intolerant of morphine, hydromorphone 0.4mg IV will be used. Further Ondansetron
4mg followed by 2 doses of Dimenhydrinate 25mg will be given for nausea and/or vomiting.
Oxygen will be used to maintain saturations greater than 93%.
Acetaminophen 975mg 6 hourly and Ibuprofen 400mg with meals three times daily will be
given.
Failure of this regime to control pain will trigger the addition of rescue analgesia.
Rescue analgesia:
Tramadol

50

100mg po Q6h prn Oxycodone 5

10mg po Q3h prn Hydromorphone

1mg sc
Q2h PRN The patients will be assessed prior to PARR discharge regarding their pain
scores at rest and on movement, and again on the morning following surgery.
4. Data Collection Data will be collected on a study sheet. Information will be kept
confidential with no patient identifiers on the form, apart from a study number. This
will reference a list kept securely by the investigators containing the patients' ULI
numbers.
The pre- and intra-operative data recorded will be: demographic (age, weight, height), the
surgical procedure, the amount of fentanyl, ephedrine and phenylephrine and propofol used.
The recovery data recorded will be: the amount of morphine or hydromorphone required, any
anti-emetics given, the maximum pain score in recovery at rest and on shoulder abduction.
After discharge from recovery, the data recorded will be: anti-emetic use, rescue analgesia
use, maximum pain score in the first 24 hours at rest and on movement.